Cyclooxygenases (COXs) are important biological mediators of inflammation that catalyze the biotransformation of arachidonic acid into prostaglandins and thromboxane (Vane, J. R. Nat. New Biol. 1971, 231:232-235). Most normal tissues express the COX-1 isoform, which performs housekeeping functions, such as maintenance of vascular tone, control of hemostasis, and cytoprotection of the gastric mucosa (Smith, W. L. et al. J. Biol. Chem. 1996, 271:33157-33160). In contrast, the inducible COX-2 isoform is overexpressed in inflammation, where it modulates edema and pain, and in neoplastic diseases, where it mediates tumor growth and potentiates metastasis (Li, G. et al. Biochem. Biophys. Res. Commun. 2002, 299:886-890). Overexpression of COX-2 is an early event of carcinogenesis, and it plays a vital role in cancer progression (Taketo, M. M. J. Natl. Cancer Inst. 1998, 90:1609). Moreover, COX-2 inhibitors have been shown to be effective adjuvant chemotherapeutic agents in some cancers (Gupta, R. A et al. Natl. Cancer Inst. 2002, 94:406-1620; Maier, T. J. et al. Biochem. Pharmacol. 2004, 67:1469-1474). Therefore, COX-2 is an ideal candidate for targeted visualization of inflammation and cancer.
Fluorocoxib A (FA), a fluorescent 5-carboxy-X-rhodamine-(5-ROX)-labeled COX-2-selective inhibitor, has been explored to visualize COX-2 in inflamed or cancerous tissues. Application of FA to detect COX-2 in the setting of inflammation and cancer (Uddin, M. J. et al. J. Cancer Res. 2010, 70:3618-3627) suggests that it may be a valuable clinical tool in these settings. However, attempts to translate it to the clinic have been hampered by its lack of solubility in aqueous solutions appropriate for human administration. All previous administrations of FA have been in 100% dimethyl sulfoxide (DMSO) or a mixed solvent consisting of DMSO (16%)/ethanol (33%)/propylene glycol (17%)/warm sterile saline (34%, 37.5° C.), that are not appropriate for human applications, especially by i.v. administration. In fact, there are many promising small molecule drugs and imaging agents, such as FA, that suffer from poor pharmacokinetics and lack of distribution to target tissues due to their hydrophobicity and/or rapid renal clearance due to low molecular weight. So what are needed are new formulations for FA, and other drug and imaging agents, which can overcome solubility challenges. The compositions and methods disclosed herein address these and other needs.